Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Richter, G; Gui, T; Bourgeois, B; Koyani, CN; Ulz, P; Heitzer, E; von, Lewinski, D; Burgering, BMT; Malle, E; Madl, T.
β-catenin regulates FOXP2 transcriptional activity via multiple binding sites.
FEBS J. 2021; 288(10):3261-3284
Doi: 10.1111/febs.15656
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- Führende Autor*innen der Med Uni Graz
- Bourgeois Benjamin Michel Rene
- Madl Tobias
- Richter Gesa Lucia
- Co-Autor*innen der Med Uni Graz
- Heitzer Ellen
- Koyani Chintan Navinchandra
- Malle Ernst
- Ulz Peter
- von Lewinski Dirk
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- Abstract:
- The transcription factor forkhead box protein P2 (FOXP2) is a highly conserved key regulator of embryonal development. The molecular mechanisms of how FOXP2 regulates embryonal development, however, remain elusive. Using RNA sequencing, we identified the Wnt signaling pathway as key target of FOXP2-dependent transcriptional regulation. Using cell-based assays, we show that FOXP2 transcriptional activity is regulated by the Wnt coregulator β-catenin and that β-catenin contacts multiple regions within FOXP2. Using nuclear magnetic resonance spectroscopy, we uncovered the molecular details of these interactions. β-catenin contacts a disordered FOXP2 region with α-helical propensity via its folded armadillo domain, whereas the intrinsically disordered β-catenin N terminus and C terminus bind to the conserved FOXP2 DNA-binding domain. Using RNA sequencing, we confirmed that β-catenin indeed regulates transcriptional activity of FOXP2 and that the FOXP2 α-helical motif acts as a key regulatory element of FOXP2 transcriptional activity. Taken together, our findings provide first insight into novel regulatory interactions and help to understand the intricate mechanisms of FOXP2 function and (mis)-regulation in embryonal development and human diseases. DATABASE: Expression data are available in the GEO database under the accession number GSE138938.
- Find related publications in this database (using NLM MeSH Indexing)
- Amino Acid Sequence - administration & dosage
- Animals - administration & dosage
- Binding Sites - administration & dosage
- Cell Line, Tumor - administration & dosage
- Cloning, Molecular - administration & dosage
- Embryo, Mammalian - administration & dosage
- Escherichia coli - genetics, metabolism
- Forkhead Transcription Factors - chemistry, genetics, metabolism
- Gene Expression Profiling - administration & dosage
- Gene Expression Regulation, Developmental - administration & dosage
- Genetic Vectors - chemistry, metabolism
- Humans - administration & dosage
- Models, Molecular - administration & dosage
- Osteoblasts - cytology, metabolism
- Protein Binding - administration & dosage
- Protein Conformation, alpha-Helical - administration & dosage
- Protein Conformation, beta-Strand - administration & dosage
- Protein Interaction Domains and Motifs - administration & dosage
- Protein Isoforms - chemistry, genetics, metabolism
- Recombinant Proteins - chemistry, genetics, metabolism
- Sequence Alignment - administration & dosage
- Sequence Homology, Amino Acid - administration & dosage
- Transcription, Genetic - administration & dosage
- Wnt Signaling Pathway - genetics
- beta Catenin - chemistry, genetics, metabolism
- Find related publications in this database (Keywords)
- FOXP2
- intrinsically disordered protein
- signal transduction
- transcriptional regulation
- Wnt signaling
- β
- ‐
- catenin